目的 探究丹参酮ⅡA(TanⅡA)减轻七氟醚(Sev)诱导的大鼠神经元细胞毒性的机制及其对AKT/FOXO3a通路产生的影响.方法 将大鼠神经元细胞HT22分为对照组、Sev组、TanⅡA干预组与Sev+Tan ⅡA+LY294002组.CCK-8实验筛选最佳TanⅡA浓度;CCK-8检测各组细胞活性;流式细胞术检测各组细胞凋亡率;试剂盒检测各组细胞MDA、SOD及GSH水平;Western blot检测各组细胞HO-1、NQO1、AKT、p-AKT、FOXO3a及p-FOXO3a的蛋白表达.结果 Tan ⅡA的最佳处理浓度为3 μg/mL.Sev能够导致细胞毒性,诱导细胞凋亡,导致氧化应激;Tan ⅡA对Sev诱导的细胞毒性、凋亡以及氧化应激具有保护作用,而抑制AKT则抵消了 Tan ⅡA对Sev诱导的细胞毒性保护作用,抵消了 Tan ⅡA对Sev诱导的细胞凋亡和氧化应激的抑制作用.此外,Tan ⅡA激活了 AKT/FOXO3a通路.结论 丹参酮ⅡA通过激活AKT/FOXO3a通路减轻七氟醚诱导的大鼠神经元细胞毒性.
Tanshinone ⅡA reduces sevoflurane-induced neuronal cytotoxicity in rats by AKT/FOXO3a pathway
Objective To investigate the mechanism of Tanshinone ⅡA(Tan ⅡA)in reducing sevoflurane(Sev)-induced neurotoxicity in rat neurons and its effect on AKT/FOXO3a pathway.Methods HT22 neurons were divided into control group,Sev group,Tan ⅡA intervention group and Sev+Tan ⅡA+LY294002 group.The optimal concentration of Tan ⅡA was screened by CCK-8 experiment;the cell viability was detected by CCK-8 experiment;the apoptosis rate was detected by flow cytometry;the levels of MDA,SOD and GSH were detected by kit;the protein expressions of HO-1,NQO1,AKT,p-AKT,FOXO3a and p-FOXO3a were detected by Western blot.Results The optimal concentration of Tan ⅡA was 3 μg/ml.Sev could cause cytotoxicity,induce apoptosis and lead to oxidative stress;Tan ⅡA had protective effects on Sev-induced cytotoxicity,apoptosis and oxidative stress,while inhibition of AKT offset the protective effects of Tan ⅡA on Sev-induced cytotoxicity,offset the inhibitory effects of Tan ⅡA on Sev-induced apoptosis and oxidative stress.In addition,Tan ⅡA activated the AKT/FOXO3a pathway.Conclusion Tan ⅡA reduces sevoflurane-induced neurotoxicity in rat neurons by activating the AKT/FOXO3a pathway.
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